Coronaviruses are among the most important causative agents of several diseases including encephalitis, hepatitis, pneumonitis, neasopharyngitis, peritonitis, and gastroenteritis in a wide variety of animal species. With respect to enteric infections, coronaviruses have been detected in the feces of man, pigs, calves, mice, rats, chickens, turkeys, dogs, cats and horses.
Canine coronavirus (CCV) enteritis was first reported in 1974 by Binn, et al., Proc. 78th Ann. Mtg.. U.S. Anim. Health Assoc. Roanoke VA Oct:359-366 (1974). The virus was isolated initially in 1971 from military dogs suffering from suspected viral gastroenteritis.
For reasons which are as yet unclear, in the late 1970's coronaviral enteritis emerged as a significant disease of dogs. The primary source of infection appears to be fecal material from infected animals. Oral infection leads to replication in the epithelial cells of the small intestine. Virus generally can be isolated from the feces of infected dogs between 3 and 14 days post-inoculation.
CCV gastroenteritis is characterized by mild depression, anorexia and loose stool with an especially offensive odor. The onset of illness is often sudden with diarrhea accompanied or shortly preceded by vomiting. Vomiting usually decreases in frequency after the first day or two of illness. The feces often contains mucous and variable amounts of blood, giving it an orange in red tint. Projectile diarrhea sometimes is seen either as a watery or bloody fluid. Young pups may become rapidly dehydrated even though fluid therapy is instituted early in the course of the illness. Deaths have occurred within as little as 24 to 36 hours after onset of clinical signs despite good supportive care. Stress seems to increase the severity of the disease. Elevated body temperatures have been observed in some cases, but most animals tend to be afebrile, and in some affected dogs, temperatures can be distinctly subnormal. See, Carmichael, "Infectious canine enteritis caused by a corona like virus," Laboratory Report, The James A. Baker Institute for Animal Health, Cornell U. 2(9) (1978).
Most affected dogs recover after week to 10 days, but dogs given early symptomatic treatment and kept warm and quiet sometimes recover more rapidly. Appel et al., Cornell Vet. 69:123-133 (1979). A persistent diarrhea for 3 to 4 weeks, that was refractory to treatment, has been reported in several instances. Appel et al., Canine Prac. 7:22-36 (1980). Concurrent ocular and nasal discharges have been noted, but their relationship to the primary infection is not known. Morphological lesions in CCV enteritis are restricted to the intestine and mesenteric lymph nodes. Histological changes are remarkably similar to those described in gnotobiotic calves infected with bovine coronavirus. Uncomplicated infection in experimental dogs is mild, and pathological changes are either not detectable or consist of dilated intestinal loops filled with watery, green-yellow fecal material. The mesenteric lymph nodes are commonly enlarged and congested or hemorrhagic.
In one case, the incubation period in experimentally infected dogs was about 24 to 36 hours. The dogs did not exhibit the typical clinical symptoms or the classic diarrhea associated with coronavirus gastroenteritis. Microscopic changes were modest, characterized by atrophy of the intestinal villi and deepening of crypts, increase in cellularity of the lamina propria, flattening of epithelial cells, and discharge of goblet cells. Keenan et al., Am. J. Vet. Res. 37:247-256 (1976). The mild symptoms may be due to the isolation procedures used for inoculatinq the experimentally infected dogs, and to the fact that the dogs were free from other major pathogens and parasites.
Specific treatment of CCV enteritis is not available. Therapy is supportive with attempts to replace fluid and electrolyte losses, control diarrhea and prevent or control secondary bacterial infections.
Serum antibody titers in dogs inoculated parenterally with CCV were higher than in orally exposed dogs. After oral challenge, the dogs responded with an anamnestic-type antibody response and shed virus for a shorter period of time than nonexposed control dogs. It appeared that local immunity, possibly mediated by IgA antibodies in the intestine, was essential for protection against CCV infection, in a manner similar to transmissible gastroenteritis in pigs. Appel et al., Canine Prac. 7:22 36 (1980).
Presumptive diagnosis of CCV enteritis is based upon clinical signs. Other causes of acute emesis and diarrhea in dogs which might also be considered include intoxications, bacterial enteritis, coccidiosis, acute pancreatitis, acute renal or hepatic failure, and other viral infections. Evidence of rapid spread is strongly suggestive of CCV enteritis. There have been several reports describing electron microscopic detection of canine parvovirus in association with CCV particles in canine fecal specimens. See, for example, Carmichael, cited above; Evermann et al., J. Am. Vet. Med. Ass. 177:784-786 (1980); Reseto et al., Arch. Virol. 66:89-93 (1980). One report detected, in addition, a canine rotavirus in one fecal specimen. McNulty et al., Vet. Res. 106:350-351 (1980). This indicates that the severity of field cases may be attributed, in part, to multiple viral infections.
Isolation of CCV from fecal specimens or intestinal contents has been reported by several investigators with some difficulties. Because of their fastidious nature and lack of susceptible cellular substrates, coronaviruses are often not isolated or diagnosed. Seroconversion or post mortem findings in fatal cases, including immunofluorescence of frozen intestinal sections all can be used for a proper etiologic diagnosis.
Coronaviruses are large (about 100 nm in diameter), enveloped, RNA viruses having a helical nucleocapsid with characteristic large club-shaped projections, or spikes, referred to as peplomers. The RNA comprises a single, linear single strand, with positive polarity, of roughly 5.5.times.10.sup.6 daltons. In ultrathin tissue sections, the virus appears, by electron microscopy, to form by budding into vacuoles in the cytoplasm. The virus is antigenically related to the Swine Transmissible Gastroenteritis Virus.
Acree et al., U.S. Pat. No. 4,567,042 and U.S. Pat. No. 4,567,043, describe an inactivated and an attenuated canine coronavirus vaccine, respectively, both comprising spent fluid medium.